15-deoxy-Delta12,14-prostaglandin J2 inhibits IFN-inducible protein 10/CXC chemokine ligand 10 expression in human microglia: mechanisms and implications - PubMed (original) (raw)

15-deoxy-Delta12,14-prostaglandin J2 inhibits IFN-inducible protein 10/CXC chemokine ligand 10 expression in human microglia: mechanisms and implications

Qiusheng Si et al. J Immunol. 2004.

Abstract

Regulation of cytokine and chemokine expression in microglia may have implications for CNS inflammatory disorders. In this study we examined the role of the cyclopentenone PG 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in microglial inflammatory activation in primary cultures of human fetal microglia. 15d-PGJ(2) potently inhibited the expression of microglial cytokines (IL-1, TNF-alpha, and IL-6). We found that 15d-PGJ(2) had differential effects on the expression of two alpha-chemokines; whereas the Glu-Lys-Arg (ELR)(-) chemokine IFN-inducible protein-10/CXCL10 was inhibited, the ELR(+) chemokine IL-8/CXCL8 was not inhibited. These findings were shown in primary human microglia and the human monocytic cells line THP-1 cells, using diverse cell stimuli such as bacterial endotoxin, proinflammatory cytokines (IL-1 and TNF-alpha), IFN-beta, and HIV-1. Furthermore, IL-8/CXCL8 expression was induced by 15d-PGJ(2) alone or in combination with TNF-alpha or HIV-1. Combined results from EMSA, Western blot analysis, and immunocytochemistry showed that 15d-PGJ(2) inhibited NF-kappaB, Stat1, and p38 MAPK activation in microglia. Adenoviral transduction of super-repressor IkappaBalpha, dominant negative MKK6, and dominant negative Ras demonstrated that NF-kappaB and p38 MAPK were involved in LPS-induced IFN-inducible protein 10/CXCL10 production. Interestingly, although LPS-induced IL-8/CXCL8 was dependent on NF-kappaB, the baseline or 15d-PGJ(2)-mediated IL-8/CXCL8 production was NF-kappaB independent. Our results demonstrate that 15d-PGJ(2) has opposing effects on the expression of two alpha-chemokines. These data may have implications for CNS inflammatory diseases.

PubMed Disclaimer

Cited by

Role of TNF-alpha during central sensitization in preclinical studies.
Andrade P, Visser-Vandewalle V, Hoffmann C, Steinbusch HW, Daemen MA, Hoogland G. Andrade P, et al. Neurol Sci. 2011 Oct;32(5):757-71. doi: 10.1007/s10072-011-0599-z. Epub 2011 May 11. Neurol Sci. 2011. PMID: 21559854 Free PMC article. Review.
TLR3 and TLR4 are innate antiviral immune receptors in human microglia: role of IRF3 in modulating antiviral and inflammatory response in the CNS.
Suh HS, Zhao ML, Choi N, Belbin TJ, Brosnan CF, Lee SC. Suh HS, et al. Virology. 2009 Sep 30;392(2):246-59. doi: 10.1016/j.virol.2009.07.001. Epub 2009 Jul 30. Virology. 2009. PMID: 19646728 Free PMC article.
The inflammatory cytokine TNFα cooperates with Ras in elevating metastasis and turns WT-Ras to a tumor-promoting entity in MCF-7 cells.
Leibovich-Rivkin T, Liubomirski Y, Meshel T, Abashidze A, Brisker D, Solomon H, Rotter V, Weil M, Ben-Baruch A. Leibovich-Rivkin T, et al. BMC Cancer. 2014 Mar 6;14:158. doi: 10.1186/1471-2407-14-158. BMC Cancer. 2014. PMID: 24598028 Free PMC article.
STAT1 and pathogens, not a friendly relationship.
Najjar I, Fagard R. Najjar I, et al. Biochimie. 2010 May;92(5):425-44. doi: 10.1016/j.biochi.2010.02.009. Epub 2010 Feb 13. Biochimie. 2010. PMID: 20159032 Free PMC article. Review.
Anti-CD45RO suppresses human immunodeficiency virus type 1 replication in microglia: role of Hck tyrosine kinase and implications for AIDS dementia.
Kim MO, Suh HS, Si Q, Terman BI, Lee SC. Kim MO, et al. J Virol. 2006 Jan;80(1):62-72. doi: 10.1128/JVI.80.1.62-72.2006. J Virol. 2006. PMID: 16352531 Free PMC article.

15-deoxy-Delta12,14-prostaglandin J2 inhibits IFN-inducible protein 10/CXC chemokine ligand 10 expression in human microglia: mechanisms and implications - PubMed (original) (raw)